The purpose of the project is to gain further understanding of the biochemical mechanisms that regulate the survival, growth, and maintenance of differentiated functions (insulin biosynthesis and secretion) in pancreatic islet B cells. These goals are best pursued in islet cells maintained in carefully controlled conditions in tissue culture in vitro. Already various hormones, cyclic nucleotides, and growth factors have been found to support islet B cell survival and replication in chemically-defined, serum-free medium. In addition, the role of cell-to-cell communication in islet hormone secretion is being studied by microfluorometry. Finally, the immunogenicity of isolated islets and islet cells has begun to be characterized, and evidence for the presence of both auto- and allogeneic determinants has been obtained in collagenase-isolated islets in mixed lymphocyte-islet cultures in vitro.